library(Biobase)
library(survminer)
library(survival)
library(tidyverse)
library(DT)
PATH <- file.path(Sys.getenv("MLAB"), "projects/brcameta/exosome/4t1_brca")
TCGAPATH <- file.path(Sys.getenv("CBM"), "TCGA-GDC/")
DPATH <- file.path(Sys.getenv("CBM"), "otherStudies/RNAseq/2023-03-22-YuhanExosomeBrCa")
do_save <- FALSE
tcga_gsva <- readRDS(file.path(PATH, "data/tcga_gsva_res.rds"))
metabric_gsva <- readRDS(file.path(PATH, "data/metabric_gsva_res.rds"))
# Signatures
all_sigs <- readRDS(file.path(PATH, "data/signatures_symbol.rds"))
all_sigs <- all_sigs[lapply(all_sigs, length) > 1]
all_sigs_human <- lapply(all_sigs, babelgene::orthologs, species = "mouse", human = FALSE)
all_sigs_human <- lapply(all_sigs_human, function(x) x %>% dplyr::pull(human_symbol))
Data Filtering
na_filter <- !is.na(tcga_gsva$vital_status)
missing_death_day_filter <- !((tcga_gsva$vital_status == "Dead") & is.na(tcga_gsva$days_to_death))
subtype_filter <- !is.na(tcga_gsva$subtype_selected)
data_filter <- na_filter & missing_death_day_filter & subtype_filter
tcga_gsva <- tcga_gsva[, data_filter]
Censoring: If samples are alive, then they lived at least as long as the day to their last followup. For 5 year threshold, those who died after 5 years, should be right-censored, and labeled to have lived at least as long as ‘days to death’ + 1.
pData(tcga_gsva) <- pData(tcga_gsva) %>%
rownames_to_column("ID") %>%
mutate(time = if_else(!is.na(days_to_death), days_to_death, days_to_last_follow_up)) %>%
mutate(time_5 = if_else(as.numeric(time) < 1825.0, as.numeric(time), 1826.0)) %>%
mutate(vital_status_1 = if_else(vital_status == "Alive", 1, 2)) %>%
mutate(vital_status_5 = if_else(vital_status == "Dead" & (time_5 > 1825.0), 1, vital_status_1)) %>%
column_to_rownames("ID")
pData(metabric_gsva) <- pData(metabric_gsva) %>%
mutate(time = OS_MONTHS * 30.437) %>%
mutate(time_5 = if_else(as.numeric(time) < 1825.0, as.numeric(time), 1826.0)) %>%
mutate(vital_status_1 = if_else(OS_STATUS == "LIVING", 1, 2)) %>%
mutate(vital_status_5 = if_else(OS_STATUS == "DECEASED" & (time_5 > 1825.0), 1, vital_status_1))
# Finding Median Thresholds
tcga_threshold_ir_c <- median(exprs(tcga_gsva["ir_c_up", ]) - exprs(tcga_gsva["ir_c_down"]))
tcga_threshold_is_c <- median(exprs(tcga_gsva["is_c_up", ]) - exprs(tcga_gsva["is_c_down", ]))
tcga_threshold_ir_is <- median(exprs(tcga_gsva["ir_is_up", ]) - exprs(tcga_gsva["ir_is_down", ]))
tcga_threshold_tgfb_c <- median(exprs(tcga_gsva["tgfb_c_up", ]) - exprs(tcga_gsva["tgfb_c_down", ]))
metabric_threshold_ir_c <- median(exprs(metabric_gsva["ir_c_up", ]) - exprs(metabric_gsva["ir_c_down"]))
metabric_threshold_is_c <- median(exprs(metabric_gsva["is_c_up", ]) - exprs(metabric_gsva["is_c_down", ]))
metabric_threshold_ir_is <- median(exprs(metabric_gsva["ir_is_up", ]) - exprs(metabric_gsva["ir_is_down", ]))
metabric_threshold_tgfb_c <- median(exprs(metabric_gsva["tgfb_c_up", ]) - exprs(metabric_gsva["tgfb_c_down", ]))
tcga_threshold_ir_c_up <- median(exprs(tcga_gsva["ir_c_up", ]))
tcga_threshold_is_c_up <- median(exprs(tcga_gsva["is_c_up", ]))
tcga_threshold_ir_is_up <- median(exprs(tcga_gsva["ir_is_up", ]))
tcga_threshold_tgfb_c_up <- median(exprs(tcga_gsva["tgfb_c_up", ]))
metabric_threshold_ir_c_up <- median(exprs(metabric_gsva["ir_c_up", ]))
metabric_threshold_is_c_up <- median(exprs(metabric_gsva["is_c_up", ]))
metabric_threshold_ir_is_up <- median(exprs(metabric_gsva["ir_is_up", ]))
metabric_threshold_tgfb_c_up <- median(exprs(metabric_gsva["tgfb_c_up", ]))
Adding GSVA data
tcga_gsva$ir_c <- t(exprs(tcga_gsva["ir_c_up", ]) - exprs(tcga_gsva["ir_c_down"]))
tcga_gsva$is_c <- t(exprs(tcga_gsva["is_c_up", ]) - exprs(tcga_gsva["is_c_down", ]))
tcga_gsva$ir_is <- t(exprs(tcga_gsva["ir_is_up", ]) - exprs(tcga_gsva["ir_is_down", ]))
tcga_gsva$tgfb_c <- t(exprs(tcga_gsva["tgfb_c_up", ]) - exprs(tcga_gsva["tgfb_c_down", ]))
tcga_gsva$ir_c_stat <- with(tcga_gsva, ifelse(tcga_gsva$ir_c <= tcga_threshold_ir_c, "low", "high"))
tcga_gsva$is_c_stat <- with(tcga_gsva, ifelse(tcga_gsva$is_c <= tcga_threshold_is_c, "low", "high"))
tcga_gsva$ir_is_stat <- with(tcga_gsva, ifelse(tcga_gsva$ir_is <= tcga_threshold_ir_is, "low", "high"))
tcga_gsva$tgfb_c_stat <- with(tcga_gsva, ifelse(tcga_gsva$tgfb_c <= tcga_threshold_tgfb_c, "low", "high"))
tcga_gsva$ir_c_up <- t(exprs(tcga_gsva["ir_c_up", ]))
tcga_gsva$is_c_up <- t(exprs(tcga_gsva["is_c_up", ]))
tcga_gsva$ir_is_up <- t(exprs(tcga_gsva["ir_is_up", ]))
tcga_gsva$tgfb_c_up <- t(exprs(tcga_gsva["tgfb_c_up", ]))
tcga_gsva$ir_c_up_stat <- with(tcga_gsva, ifelse(tcga_gsva$ir_c_up <= tcga_threshold_ir_c_up, "low", "high"))
tcga_gsva$is_c_up_stat <- with(tcga_gsva, ifelse(tcga_gsva$is_c_up <= tcga_threshold_is_c_up, "low", "high"))
tcga_gsva$ir_is_up_stat <- with(tcga_gsva, ifelse(tcga_gsva$ir_is_up <= tcga_threshold_ir_is_up, "low", "high"))
tcga_gsva$tgfb_c_up_stat <- with(tcga_gsva, ifelse(tcga_gsva$tgfb_c_up <= tcga_threshold_tgfb_c_up, "low", "high"))
metabric_gsva$ir_c <- t(exprs(metabric_gsva["ir_c_up", ]) - exprs(metabric_gsva["ir_c_down"]))
metabric_gsva$is_c <- t(exprs(metabric_gsva["is_c_up", ]) - exprs(metabric_gsva["is_c_down", ]))
metabric_gsva$ir_is <- t(exprs(metabric_gsva["ir_is_up", ]) - exprs(metabric_gsva["ir_is_down", ]))
metabric_gsva$tgfb_c <- t(exprs(metabric_gsva["tgfb_c_up", ]) - exprs(metabric_gsva["tgfb_c_down", ]))
metabric_gsva$ir_c_stat <- with(metabric_gsva, ifelse(metabric_gsva$ir_c <= metabric_threshold_ir_c, "low", "high"))
metabric_gsva$is_c_stat <- with(metabric_gsva, ifelse(metabric_gsva$is_c <= metabric_threshold_is_c, "low", "high"))
metabric_gsva$ir_is_stat <- with(metabric_gsva, ifelse(metabric_gsva$ir_is <= metabric_threshold_ir_is, "low", "high"))
metabric_gsva$tgfb_c_stat <- with(tcga_gsva, ifelse(metabric_gsva$tgfb_c <= metabric_threshold_tgfb_c, "low", "high"))
metabric_gsva$ir_c_up <- t(exprs(metabric_gsva["ir_c_up", ]))
metabric_gsva$is_c_up <- t(exprs(metabric_gsva["is_c_up", ]))
metabric_gsva$ir_is_up <- t(exprs(metabric_gsva["ir_is_up", ]))
metabric_gsva$tgfb_c_up <- t(exprs(metabric_gsva["tgfb_c_up", ]))
metabric_gsva$ir_c_up_stat <- with(metabric_gsva, ifelse(metabric_gsva$ir_c_up <= metabric_threshold_ir_c_up, "low", "high"))
metabric_gsva$is_c_up_stat <- with(metabric_gsva, ifelse(metabric_gsva$is_c_up <= metabric_threshold_is_c_up, "low", "high"))
metabric_gsva$ir_is_up_stat <- with(metabric_gsva, ifelse(metabric_gsva$ir_is_up <= metabric_threshold_ir_is_up, "low", "high"))
metabric_gsva$tgfb_c_up_stat <- with(metabric_gsva, ifelse(metabric_gsva$tgfb_c_up <= metabric_threshold_tgfb_c_up, "low", "high"))
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$ir_c_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$ir_c_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$ir_c_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$ir_c_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$ir_c_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$ir_c_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$ir_c_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$ir_c_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$is_c_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$is_c_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$is_c_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$is_c_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$is_c_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$is_c_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$is_c_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$is_c_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$ir_is_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$ir_is_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$ir_is_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$ir_is_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$ir_is_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$ir_is_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$ir_is_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$ir_is_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$tgfb_c_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$tgfb_c_up_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$tgfb_c_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$tgfb_c_up_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time), tcga_gsva$vital_status_1) ~ tcga_gsva$tgfb_c_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva$time_5), tcga_gsva$vital_status_5) ~ tcga_gsva$tgfb_c_stat),
data = tcga_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time), metabric_gsva$vital_status_1) ~ metabric_gsva$tgfb_c_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva$time_5), metabric_gsva$vital_status_5) ~ metabric_gsva$tgfb_c_stat),
data = metabric_gsva,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
# Thresholds
tcga_basal_filter <- tcga_gsva$subtype_selected == "BRCA.Basal"
tcga_gsva_basal <- tcga_gsva[, tcga_basal_filter]
metabric_basal_filter <- metabric_gsva$Pam50_SUBTYPE == "Basal"
metabric_gsva_basal <- metabric_gsva[, metabric_basal_filter]
tcga_threshold_ir_c <- median(exprs(tcga_gsva_basal["ir_c_up", ]) - exprs(tcga_gsva_basal["ir_c_down", ]))
tcga_threshold_is_c <- median(exprs(tcga_gsva_basal["is_c_up", ]) - exprs(tcga_gsva_basal["is_c_down", ]))
tcga_threshold_ir_is <- median(exprs(tcga_gsva_basal["ir_is_up", ]) - exprs(tcga_gsva_basal["ir_is_down", ]))
tcga_threshold_tgfb_c <- median(exprs(tcga_gsva_basal["tgfb_c_up", ]) - exprs(tcga_gsva_basal["tgfb_c_down", ]))
metabric_threshold_ir_c <- median(exprs(metabric_gsva_basal["ir_c_up", ]) - exprs(metabric_gsva_basal["ir_c_down", ]))
metabric_threshold_is_c <- median(exprs(metabric_gsva_basal["is_c_up", ]) - exprs(metabric_gsva_basal["is_c_down", ]))
metabric_threshold_ir_is <- median(exprs(metabric_gsva_basal["ir_is_up", ]) - exprs(metabric_gsva_basal["ir_is_down", ]))
metabric_threshold_tgfb_c <- median(exprs(metabric_gsva_basal["tgfb_c_up", ]) - exprs(metabric_gsva_basal["tgfb_c_down", ]))
tcga_threshold_ir_c_up <- median(exprs(tcga_gsva_basal["ir_c_up", ]))
tcga_threshold_is_c_up <- median(exprs(tcga_gsva_basal["is_c_up", ]))
tcga_threshold_ir_is_up <- median(exprs(tcga_gsva_basal["ir_is_up", ]))
tcga_threshold_tgfb_c_up <- median(exprs(tcga_gsva_basal["tgfb_c_up", ]))
metabric_threshold_ir_c_up <- median(exprs(metabric_gsva_basal["ir_c_up", ]))
metabric_threshold_is_c_up <- median(exprs(metabric_gsva_basal["is_c_up", ]))
metabric_threshold_ir_is_up <- median(exprs(metabric_gsva_basal["ir_is_up", ]))
metabric_threshold_tgfb_c_up <- median(exprs(metabric_gsva_basal["tgfb_c_up", ]))
Adding GSVA data
tcga_gsva_basal$ir_c <- t(exprs(tcga_gsva_basal["ir_c_up", ]) - exprs(tcga_gsva_basal["ir_c_down", ]))
tcga_gsva_basal$is_c <- t(exprs(tcga_gsva_basal["is_c_up", ]) - exprs(tcga_gsva_basal["is_c_down", ]))
tcga_gsva_basal$ir_is <- t(exprs(tcga_gsva_basal["ir_is_up", ]) - exprs(tcga_gsva_basal["ir_is_down", ]))
tcga_gsva_basal$tgfb_c <- t(exprs(tcga_gsva_basal["tgfb_c_up", ]) - exprs(tcga_gsva_basal["tgfb_c_down", ]))
metabric_gsva_basal$ir_c <- t(exprs(metabric_gsva_basal["ir_c_up", ]) - exprs(metabric_gsva_basal["ir_c_down", ]))
metabric_gsva_basal$is_c <- t(exprs(metabric_gsva_basal["is_c_up", ]) - exprs(metabric_gsva_basal["is_c_down", ]))
metabric_gsva_basal$ir_is <- t(exprs(metabric_gsva_basal["ir_is_up", ]) - exprs(metabric_gsva_basal["ir_is_down", ]))
metabric_gsva_basal$tgfb_c <- t(exprs(metabric_gsva_basal["tgfb_c_up", ]) - exprs(metabric_gsva_basal["tgfb_c_down", ]))
tcga_gsva_basal$ir_c_up <- t(exprs(tcga_gsva_basal["ir_c_up", ]))
tcga_gsva_basal$is_c_up <- t(exprs(tcga_gsva_basal["is_c_up", ]))
tcga_gsva_basal$ir_is_up <- t(exprs(tcga_gsva_basal["ir_is_up", ]))
tcga_gsva_basal$tgfb_c_up <- t(exprs(tcga_gsva_basal["tgfb_c_up", ]))
metabric_gsva_basal$ir_c_up <- t(exprs(metabric_gsva_basal["ir_c_up", ]))
metabric_gsva_basal$is_c_up <- t(exprs(metabric_gsva_basal["is_c_up", ]))
metabric_gsva_basal$ir_is_up <- t(exprs(metabric_gsva_basal["ir_is_up", ]))
metabric_gsva_basal$tgfb_c_up <- t(exprs(metabric_gsva_basal["tgfb_c_up", ]))
tcga_gsva_basal$ir_c_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$ir_c <= tcga_threshold_ir_c, "low", "high"))
tcga_gsva_basal$is_c_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$is_c <= tcga_threshold_is_c, "low", "high"))
tcga_gsva_basal$ir_is_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$ir_is <= tcga_threshold_ir_is, "low", "high"))
tcga_gsva_basal$tgfb_c_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$tgfb_c <= tcga_threshold_tgfb_c, "low", "high"))
tcga_gsva_basal$ir_c_up_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$ir_c_up <= tcga_threshold_ir_c_up, "low", "high"))
tcga_gsva_basal$is_c_up_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$is_c_up <= tcga_threshold_is_c_up, "low", "high"))
tcga_gsva_basal$ir_is_up_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$ir_is_up <= tcga_threshold_ir_is_up, "low", "high"))
tcga_gsva_basal$tgfb_c_up_stat <- with(tcga_gsva_basal, ifelse(tcga_gsva_basal$tgfb_c_up <= tcga_threshold_tgfb_c_up, "low", "high"))
metabric_gsva_basal$ir_c_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$ir_c <= metabric_threshold_ir_c, "low", "high"))
metabric_gsva_basal$is_c_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$is_c <= metabric_threshold_is_c, "low", "high"))
metabric_gsva_basal$ir_is_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$ir_is <= metabric_threshold_ir_is, "low", "high"))
metabric_gsva_basal$tgfb_c_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$tgfb_c <= metabric_threshold_tgfb_c, "low", "high"))
metabric_gsva_basal$ir_c_up_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$ir_c_up <= metabric_threshold_ir_c_up, "low", "high"))
metabric_gsva_basal$is_c_up_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$is_c_up <= metabric_threshold_is_c_up, "low", "high"))
metabric_gsva_basal$ir_is_up_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$ir_is_up <= metabric_threshold_ir_is_up, "low", "high"))
metabric_gsva_basal$tgfb_c_up_stat <- with(metabric_gsva_basal, ifelse(metabric_gsva_basal$tgfb_c_up <= metabric_threshold_tgfb_c_up, "low", "high"))
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$ir_c_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$ir_c_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$ir_c_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$ir_c_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$ir_c_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$ir_c_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$ir_c_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$ir_c_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$is_c_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$is_c_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$is_c_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$is_c_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$is_c_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$is_c_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$is_c_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$is_c_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$ir_is_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$ir_is_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$ir_is_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$ir_is_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$ir_is_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$ir_is_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$ir_is_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$ir_is_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "Metabric w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$tgfb_c_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$tgfb_c_up_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$tgfb_c_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$tgfb_c_up_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time), tcga_gsva_basal$vital_status_1) ~ tcga_gsva_basal$tgfb_c_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(tcga_gsva_basal$time_5), tcga_gsva_basal$vital_status_5) ~ tcga_gsva_basal$tgfb_c_stat),
data = tcga_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "TCGA w/ 5-year threshold"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time), metabric_gsva_basal$vital_status_1) ~ metabric_gsva_basal$tgfb_c_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC"
)
ggsurvplot(
fit = survfit(Surv(as.numeric(metabric_gsva_basal$time_5), metabric_gsva_basal$vital_status_5) ~ metabric_gsva_basal$tgfb_c_stat),
data = metabric_gsva_basal,
xlab = "Days",
ylab = "Overall survival probability",
conf.int = TRUE,
pval = TRUE,
title = "METABRIC w/ 5-year threshold"
)
TCGA
pData(tcga_gsva)$subtype_selected <- relevel(factor(pData(tcga_gsva)$subtype_selected), "BRCA.Normal")
tcga.cox1 <- coxph(Surv(as.numeric(time), vital_status_1) ~ subtype_selected, data = pData(tcga_gsva))
tcga.cox2 <- coxph(Surv(as.numeric(time), vital_status_1) ~ ir_is + subtype_selected, data = pData(tcga_gsva))
tcga.cox3 <- coxph(Surv(as.numeric(time), vital_status_1) ~ ir_is + subtype_selected + age_at_index, data = pData(tcga_gsva))
anova(tcga.cox1, tcga.cox2, tcga.cox3)
summary(tcga.cox3)
## Call:
## coxph(formula = Surv(as.numeric(time), vital_status_1) ~ ir_is +
## subtype_selected + age_at_index, data = pData(tcga_gsva))
##
## n= 1208, number of events= 199
##
## coef exp(coef) se(coef) z Pr(>|z|)
## ir_is -0.16597 0.84707 0.20608 -0.805 0.4206
## subtype_selectedBRCA.Basal -0.57840 0.56080 0.25338 -2.283 0.0224 *
## subtype_selectedBRCA.Her2 0.03178 1.03229 0.30946 0.103 0.9182
## subtype_selectedBRCA.LumA -0.89462 0.40876 0.20735 -4.315 1.60e-05 ***
## subtype_selectedBRCA.LumB -0.38217 0.68238 0.28427 -1.344 0.1788
## age_at_index 0.03465 1.03525 0.00563 6.154 7.54e-10 ***
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## exp(coef) exp(-coef) lower .95 upper .95
## ir_is 0.8471 1.1805 0.5656 1.2686
## subtype_selectedBRCA.Basal 0.5608 1.7832 0.3413 0.9215
## subtype_selectedBRCA.Her2 1.0323 0.9687 0.5628 1.8933
## subtype_selectedBRCA.LumA 0.4088 2.4464 0.2723 0.6137
## subtype_selectedBRCA.LumB 0.6824 1.4655 0.3909 1.1912
## age_at_index 1.0353 0.9659 1.0239 1.0467
##
## Concordance= 0.696 (se = 0.022 )
## Likelihood ratio test= 67.52 on 6 df, p=1e-12
## Wald test = 70.84 on 6 df, p=3e-13
## Score (logrank) test = 72.85 on 6 df, p=1e-13
Metabric
pData(metabric_gsva)$Pam50_SUBTYPE <- relevel(factor(pData(metabric_gsva)$Pam50_SUBTYPE), "Normal")
metabric.cox1 <- coxph(Surv(as.numeric(time), vital_status_1) ~ Pam50_SUBTYPE, data = pData(metabric_gsva))
metabric.cox2 <- coxph(Surv(as.numeric(time), vital_status_1) ~ ir_is + Pam50_SUBTYPE, data = pData(metabric_gsva))
metabric.cox3 <- coxph(Surv(as.numeric(time), vital_status_1) ~ ir_is + Pam50_SUBTYPE + AGE_AT_DIAGNOSIS, data = pData(metabric_gsva))
anova(metabric.cox1, metabric.cox2, metabric.cox3)
summary(metabric.cox3)
## Call:
## coxph(formula = Surv(as.numeric(time), vital_status_1) ~ ir_is +
## Pam50_SUBTYPE + AGE_AT_DIAGNOSIS, data = pData(metabric_gsva))
##
## n= 1980, number of events= 1143
##
## coef exp(coef) se(coef) z Pr(>|z|)
## ir_is 0.056306 1.057922 0.087440 0.644 0.5196
## Pam50_SUBTYPEBasal 0.211357 1.235353 0.128448 1.645 0.0999 .
## Pam50_SUBTYPEHer2 0.301280 1.351588 0.131973 2.283 0.0224 *
## Pam50_SUBTYPELumA -0.222111 0.800826 0.117074 -1.897 0.0578 .
## Pam50_SUBTYPELumB 0.088125 1.092124 0.127894 0.689 0.4908
## Pam50_SUBTYPENC 0.114633 1.121462 0.460122 0.249 0.8033
## AGE_AT_DIAGNOSIS 0.036491 1.037165 0.002729 13.371 <2e-16 ***
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## exp(coef) exp(-coef) lower .95 upper .95
## ir_is 1.0579 0.9452 0.8913 1.256
## Pam50_SUBTYPEBasal 1.2354 0.8095 0.9604 1.589
## Pam50_SUBTYPEHer2 1.3516 0.7399 1.0435 1.751
## Pam50_SUBTYPELumA 0.8008 1.2487 0.6366 1.007
## Pam50_SUBTYPELumB 1.0921 0.9156 0.8500 1.403
## Pam50_SUBTYPENC 1.1215 0.8917 0.4551 2.763
## AGE_AT_DIAGNOSIS 1.0372 0.9642 1.0316 1.043
##
## Concordance= 0.611 (se = 0.009 )
## Likelihood ratio test= 233.5 on 7 df, p=<2e-16
## Wald test = 223.3 on 7 df, p=<2e-16
## Score (logrank) test = 228.2 on 7 df, p=<2e-16